{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T22:28:40Z","timestamp":1793312920076,"version":"4.5.0"},"reference-count":46,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["BX005120"],"award-info":[{"award-number":["BX005120"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"U.S. Department of Health & Human Services | NIH | National Cancer Institute","doi-asserted-by":"publisher","award":["P30CA134274"],"award-info":[{"award-number":["P30CA134274"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"U.S. Department of Health & Human Services | NIH | National Cancer Institute","doi-asserted-by":"publisher","award":["P30CA006973"],"award-info":[{"award-number":["P30CA006973"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"U.S. Department of Health & Human Services | NIH | National Cancer Institute","doi-asserted-by":"publisher","award":["R01CA277031"],"award-info":[{"award-number":["R01CA277031"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"U.S. Department of Health & Human Services | NIH | National Cancer Institute","doi-asserted-by":"publisher","award":["U01CA271412"],"award-info":[{"award-number":["U01CA271412"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"U.S. Department of Health & Human Services | NIH | National Cancer Institute","doi-asserted-by":"publisher","award":["U54CA224019"],"award-info":[{"award-number":["U54CA224019"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000048","name":"American Cancer Society","doi-asserted-by":"publisher","award":["MRSG-17-040-01-LIB"],"award-info":[{"award-number":["MRSG-17-040-01-LIB"]}],"id":[{"id":"10.13039\/100000048","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Leukemia"],"published-print":{"date-parts":[[2026,8]]},"DOI":"10.1038\/s41375-026-02982-7","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T14:39:03Z","timestamp":1780411143000},"page":"1636-1646","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Sphingosine-1-phosphate receptor modulators resensitize FLT3-ITD acute myeloid leukemia cells with NRAS mutations to FLT3 inhibitors"],"prefix":"10.1038","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0595-3866","authenticated-orcid":false,"given":"Aditi","family":"Chatterjee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moaath K.","family":"Mustafa Ali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher M.","family":"Bailey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchen","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald","family":"Small","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0160-7026","authenticated-orcid":false,"given":"Catherine C.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8844-2345","authenticated-orcid":false,"given":"Elie","family":"Traer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4749-3768","authenticated-orcid":false,"given":"Yin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5911-6997","authenticated-orcid":false,"given":"Giovannino","family":"Silvestri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9499-1348","authenticated-orcid":false,"given":"Maria R.","family":"Baer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,2]]},"reference":[{"key":"2982_CR1","doi-asserted-by":"publisher","first-page":"1079","DOI":"10.1056\/NEJMoa1112304","volume":"366","author":"JP Patel","year":"2012","unstructured":"Patel JP, G\u00f6nen M, Figueroa ME, Fernandez H, Sun Z, Racevskis J, et al. Prognostic relevance of integrated genetic profiling in acute myeloid leukemia. N Engl J Med. 2012;366:1079\u201389.","journal-title":"N Engl J Med"},{"key":"2982_CR2","doi-asserted-by":"publisher","first-page":"2209","DOI":"10.1056\/NEJMoa1516192","volume":"374","author":"E Papaemmanuil","year":"2016","unstructured":"Papaemmanuil E, Gerstung M, Bullinger L, Gaidzik VI, Paschka P, Roberts ND, et al. Genomic classification and prognosis in acute myeloid leukemia. N Engl J Med. 2016;374:2209\u201321.","journal-title":"N Engl J Med"},{"key":"2982_CR3","first-page":"2140","volume":"9","author":"K Spiekermann","year":"2003","unstructured":"Spiekermann K, Bagrintseva K, Schwab R, Schmieja K, Hiddemann W. Overexpression and constitutive activation of FLT3 induces STAT5 activation in primary acute myeloid leukemia blast cells. Clin Cancer Res. 2003;9:2140\u201350.","journal-title":"Clin Cancer Res"},{"key":"2982_CR4","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1002\/ajh.26451","volume":"97","author":"PK Reville","year":"2022","unstructured":"Reville PK, Sasaki K, Kantarjian HM, Daver NG, Yilmaz M, Dinardo CD, et al. Improved outcomes among newly diagnosed patients with FMS-like tyrosine kinase 3 internal tandem duplication mutated acute myeloid leukemia treated with contemporary therapy: revisiting the European LeukemiaNet adverse risk classification. Am J Hematol. 2022;97:329\u201337.","journal-title":"Am J Hematol"},{"key":"2982_CR5","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.35813","volume":"131","author":"A Bazinet","year":"2025","unstructured":"Bazinet A, Bataller A, Kadia T, Daver N, Short NJ, Yilmaz M, et al. A retrospective study of outcomes across time and treatment regimens in newly diagnosed, FMS-like tyrosine kinase 3 (FLT3)-mutated acute myeloid leukemia. Cancer. 2025;131:e35813.","journal-title":"Cancer"},{"key":"2982_CR6","doi-asserted-by":"publisher","first-page":"1728","DOI":"10.1056\/NEJMoa1902688","volume":"381","author":"AE Perl","year":"2019","unstructured":"Perl AE, Martinelli G, Cortes JE, Neubauer A, Berman E, Paolini S, et al. Gilteritinib or chemotherapy for relapsed or refractory FLT3-mutated AML. N Engl J Med. 2019;381:1728\u201340.","journal-title":"N Engl J Med"},{"key":"2982_CR7","doi-asserted-by":"publisher","first-page":"528","DOI":"10.1007\/s12185-023-03681-0","volume":"120","author":"VE Kennedy","year":"2024","unstructured":"Kennedy VE, Smith CC. FLT3 targeting in the modern era: from clonal selection to combination therapies. Int J Hematol. 2024;120:528\u201340.","journal-title":"Int J Hematol"},{"key":"2982_CR8","doi-asserted-by":"publisher","first-page":"1643","DOI":"10.1182\/blood-2006-05-023804","volume":"109","author":"O Piloto","year":"2007","unstructured":"Piloto O, Wright M, Brown P, Kim KT, Levis M, Small D. Prolonged exposure to FLT3 inhibitors leads to resistance via activation of parallel signaling pathways. Blood. 2007;109:1643\u201352.","journal-title":"Blood"},{"key":"2982_CR9","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-08263-x","volume":"10","author":"H Zhang","year":"2019","unstructured":"Zhang H, Savage S, Schultz AR, Bottomly D, White L, Segerdell E, et al. Clinical resistance to crenolanib in acute myeloid leukemia due to diverse molecular mechanisms. Nat Commun. 2019;10:244.","journal-title":"Nat Commun"},{"key":"2982_CR10","doi-asserted-by":"publisher","first-page":"1050","DOI":"10.1158\/2159-8290.CD-18-1453","volume":"9","author":"CM McMahon","year":"2019","unstructured":"McMahon CM, Ferng T, Canaani J, Wang ES, Morrissette JJD, Eastburn DJ, et al. Clonal Selection with RAS pathway activation mediates secondary clinical resistance to selective FLT3 inhibition in acute myeloid leukemia. Cancer Discov. 2019;9:1050\u201363.","journal-title":"Cancer Discov"},{"key":"2982_CR11","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1158\/2643-3230.BCD-20-0143","volume":"2","author":"AS Alotaibi","year":"2021","unstructured":"Alotaibi AS, Yilmaz M, Kanagal-Shamanna R, Loghavi S, Kadia TM, DiNardo CD, et al. Patterns of resistance differ in patients with acute myeloid leukemia treated with type I versus type II FLT3 inhibitors. Blood Cancer Discov. 2021;2:125\u201334.","journal-title":"Blood Cancer Discov"},{"key":"2982_CR12","doi-asserted-by":"publisher","first-page":"2144","DOI":"10.1182\/bloodadvances.2021006489","volume":"6","author":"CC Smith","year":"2022","unstructured":"Smith CC, Levis MJ, Perl AE, Hill JE, Rosales M, Bahceci E. Molecular profile of FLT3-mutated relapsed\/refractory patients with AML in the phase 3 ADMIRAL study of gilteritinib. Blood Adv. 2022;6:2144\u201355.","journal-title":"Blood Adv"},{"key":"2982_CR13","doi-asserted-by":"publisher","first-page":"999","DOI":"10.1016\/j.ccell.2021.06.003","volume":"39","author":"SK Joshi","year":"2021","unstructured":"Joshi SK, Nechiporuk T, Bottomly D, Piehowski PD, Reisz JA, Pittsenbarger J, et al. The AML microenvironment catalyzes a stepwise evolution to gilteritinib resistance. Cancer Cell. 2021;39:999\u20131014.e8.","journal-title":"Cancer Cell"},{"key":"2982_CR14","doi-asserted-by":"publisher","first-page":"2457","DOI":"10.1158\/0008-5472.CAN-11-2612","volume":"72","author":"IA Prior","year":"2012","unstructured":"Prior IA, Lewis PD, Mattos C. A comprehensive survey of Ras mutations in cancer. Cancer Res. 2012;72:2457\u201367.","journal-title":"Cancer Res"},{"key":"2982_CR15","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1158\/1535-7163.MCT-16-0876","volume":"16","author":"M Larrosa-Garcia","year":"2017","unstructured":"Larrosa-Garcia M, Baer MR. FLT3 inhibitors in acute myeloid leukemia: current status and future directions. Mol Cancer Ther. 2017;16:991\u20131001.","journal-title":"Mol Cancer Ther"},{"key":"2982_CR16","doi-asserted-by":"publisher","first-page":"31794","DOI":"10.1074\/jbc.M112.385765","volume":"287","author":"CR Gault","year":"2012","unstructured":"Gault CR, Eblen ST, Neumann CA, Hannun YA, Obeid LM. Oncogenic K-Ras regulates bioactive sphingolipids in a sphingosine kinase 1-dependent manner. J Biol Chem. 2012;287:31794\u2013803.","journal-title":"J Biol Chem"},{"key":"2982_CR17","doi-asserted-by":"publisher","first-page":"2619","DOI":"10.1038\/onc.2016.428","volume":"36","author":"W Zhu","year":"2017","unstructured":"Zhu W, Gliddon BL, Jarman KE, Moretti PAB, Tin T, Parise LV, et al. CIB1 contributes to oncogenic signalling by Ras via modulating the subcellular localisation of sphingosine kinase 1. Oncogene. 2017;36:2619\u201327.","journal-title":"Oncogene"},{"key":"2982_CR18","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1158\/1535-7163.MCT-20-0663","volume":"20","author":"M Scarpa","year":"2021","unstructured":"Scarpa M, Singh P, Bailey CM, Lee JK, Kapoor S, Lapidus RG, et al. PP2A-activating drugs enhance FLT3 inhibitor efficacy through AKT inhibition-dependent GSK-3\u03b2-mediated c-Myc and Pim-1 proteasomal degradation. Mol Cancer Ther. 2021;20:676\u201390.","journal-title":"Mol Cancer Ther"},{"key":"2982_CR19","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1158\/2767-9764.CRC-23-0379","volume":"4","author":"JK Lee","year":"2024","unstructured":"Lee JK, Chatterjee A, Scarpa M, Bailey CM, Niyongere S, Singh P, et al. Pim kinase inhibitors increase gilteritinib cytotoxicity in FLT3-ITD acute myeloid leukemia through GSK-3\u03b2 activation and c-Myc and Mcl-1 proteasomal degradation. Cancer Res Commun. 2024;4:431\u201345.","journal-title":"Cancer Res Commun"},{"key":"2982_CR20","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1158\/0008-5472.CAN-09-1947","volume":"70","author":"TC Chou","year":"2010","unstructured":"Chou TC. Drug combination studies and their synergy quantification using the Chou-Talalay method. Cancer Res. 2010;70:440\u20136.","journal-title":"Cancer Res"},{"key":"2982_CR21","doi-asserted-by":"publisher","first-page":"2408","DOI":"10.1172\/JCI31095","volume":"117","author":"P Neviani","year":"2007","unstructured":"Neviani P, Santhanam R, Oaks JJ, Eiring AM, Notari M, Blaser BW, et al. FTY720, a new alternative for treating blast crisis chronic myelogenous leukemia and Philadelphia chromosome-positive acute lymphocytic leukemia. J Clin Invest. 2007;117:2408\u201321.","journal-title":"J Clin Invest"},{"key":"2982_CR22","doi-asserted-by":"publisher","first-page":"2092","DOI":"10.1158\/1078-0432.CCR-13-2575","volume":"20","author":"A Agarwal","year":"2014","unstructured":"Agarwal A, MacKenzie RJ, Pippa R, Eide CA, Oddo J, Tyner JW, et al. Antagonism of SET using OP449 enhances the efficacy of tyrosine kinase inhibitors and overcomes drug resistance in myeloid leukemia. Clin Cancer Res. 2014;20:2092\u2013103.","journal-title":"Clin Cancer Res"},{"key":"2982_CR23","doi-asserted-by":"publisher","first-page":"47465","DOI":"10.18632\/oncotarget.10167","volume":"7","author":"AM Smith","year":"2016","unstructured":"Smith AM, Dun MD, Lee EM, Harrison C, Kahl R, Flanagan H, et al. Activation of protein phosphatase 2A in FLT3+ acute myeloid leukemia cells enhances the cytotoxicity of FLT3 tyrosine kinase inhibitors. Oncotarget. 2016;7:47465\u201378.","journal-title":"Oncotarget"},{"key":"2982_CR24","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-024-01774-9","volume":"22","author":"L Jiang","year":"2024","unstructured":"Jiang L, Zhao Y, Liu F, Huang Y, Zhang Y, Yuan B, et al. Concomitant targeting of FLT3 and SPHK1 exerts synergistic cytotoxicity in FLT3-ITD+ acute myeloid leukemia by inhibiting \u03b2-catenin activity via the PP2A-GSK3\u03b2 axis. Cell Commun Signal. 2024;22:391.","journal-title":"Cell Commun Signal"},{"key":"2982_CR25","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/j.yexcr.2015.02.025","volume":"333","author":"J Newton","year":"2015","unstructured":"Newton J, Lima S, Maceyka M, Spiegel S. Revisiting the sphingolipid rheostat: evolving concepts in cancer therapy. Exp Cell Res. 2015;333:195\u2013200.","journal-title":"Exp Cell Res"},{"key":"2982_CR26","first-page":"132","volume":"39","author":"AD Cox","year":"2025","unstructured":"Cox AD, Der CJ. \u201cUndruggable KRAS\u201d: druggable after all. Genes Dev. 2025;39:132\u201362.","journal-title":"Genes Dev"},{"key":"2982_CR27","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1097\/CAD.0000000000000358","volume":"27","author":"AK Enjeti","year":"2016","unstructured":"Enjeti AK, D\u2019Crus A, Melville K, Verrills NM, Rowlings P. A systematic evaluation of the safety and toxicity of fingolimod for its potential use in the treatment of acute myeloid leukaemia. Anticancer Drugs. 2016;27:560\u20138.","journal-title":"Anticancer Drugs"},{"key":"2982_CR28","doi-asserted-by":"publisher","first-page":"1184","DOI":"10.1016\/S0140-6736(21)00244-0","volume":"398","author":"MP McGinley","year":"2021","unstructured":"McGinley MP, Cohen JA. Sphingosine 1-phosphate receptor modulators in multiple sclerosis and other conditions. Lancet. 2021;398:1184\u201394.","journal-title":"Lancet"},{"key":"2982_CR29","doi-asserted-by":"publisher","first-page":"41.e1","DOI":"10.1016\/j.jtct.2022.10.029","volume":"29","author":"S Dertschnig","year":"2023","unstructured":"Dertschnig S, Gergely P, Finke J, Schanz U, Holler E, Holtick U, et al. Mocravimod, a selective sphingosine-1-phosphate receptor modulator, in allogeneic hematopoietic stem cell transplantation for malignancy. Transplant Cell Ther. 2023;29:41.e1\u201341.e9.","journal-title":"Transplant Cell Ther"},{"key":"2982_CR30","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1111\/bjh.12599","volume":"164","author":"X Yang","year":"2014","unstructured":"Yang X, Sexauer A, Levis M. Bone marrow stroma-mediated resistance to FLT3 inhibitors in FLT3-ITD AML is mediated by persistent activation of extracellular regulated kinase. Br J Haematol. 2014;164:61\u201372.","journal-title":"Br J Haematol"},{"key":"2982_CR31","doi-asserted-by":"publisher","first-page":"5554","DOI":"10.1158\/0008-5472.CAN-16-2593","volume":"77","author":"JK Bruner","year":"2017","unstructured":"Bruner JK, Ma HS, Li L, Qin ACR, Rudek MA, Jones RJ, et al. Adaptation to TKI treatment reactivates ERK signaling in tyrosine kinase-driven leukemias and other malignancies. Cancer Res. 2017;77:5554\u201363.","journal-title":"Cancer Res"},{"key":"2982_CR32","doi-asserted-by":"publisher","first-page":"1527","DOI":"10.1016\/S0960-9822(00)00834-4","volume":"10","author":"P Xia","year":"2000","unstructured":"Xia P, Gamble JR, Wang L, Pitson SM, Moretti PA, Wattenberg BW, et al. An oncogenic role of sphingosine kinase. Curr Biol. 2000;10:1527\u201330.","journal-title":"Curr Biol"},{"key":"2982_CR33","doi-asserted-by":"publisher","first-page":"3364","DOI":"10.1038\/onc.2013.303","volume":"33","author":"V Albinet","year":"2014","unstructured":"Albinet V, Bats ML, Huwiler A, Rochaix P, Chevreau C, S\u00e9gui B, et al. Dual role of sphingosine kinase-1 in promoting the differentiation of dermal fibroblasts and the dissemination of melanoma cells. Oncogene. 2014;33:3364\u201373.","journal-title":"Oncogene"},{"key":"2982_CR34","doi-asserted-by":"publisher","first-page":"1944","DOI":"10.1182\/blood-2016-04-708750","volume":"128","author":"M Dany","year":"2016","unstructured":"Dany M, Gencer S, Nganga R, Thomas RJ, Oleinik N, Baron KD, et al. Targeting FLT3-ITD signaling mediates ceramide-dependent mitophagy and attenuates drug resistance in AML. Blood. 2016;128:1944\u201358.","journal-title":"Blood"},{"key":"2982_CR35","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1080\/1120009X.2025.2478340","volume":"38","author":"M Tecik","year":"2026","unstructured":"Tecik M, Adan A. Concurrent inhibition of FLT3 and sphingosine kinase-1 triggers synergistic cytotoxicity in midostaurin resistant FLT3-ITD positive acute myeloid leukemia cells via blocking FLT3\/STAT5A signalling to induce apoptosis. J Chemother. 2026;38:145\u201361.","journal-title":"J Chemother"},{"key":"2982_CR36","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.cell.2017.06.009","volume":"170","author":"DK Simanshu","year":"2017","unstructured":"Simanshu DK, Nissley DV, McCormick F. RAS proteins and their regulators in human disease. Cell. 2017;170:17\u201333.","journal-title":"Cell"},{"key":"2982_CR37","doi-asserted-by":"publisher","first-page":"1207","DOI":"10.1056\/NEJMoa1917239","volume":"383","author":"DS Hong","year":"2020","unstructured":"Hong DS, Fakih MG, Strickler JH, Desai J, Durm GA, Shapiro GI, et al. KRASG12C inhibition with sotorasib in advanced solid tumors. N Engl J Med. 2020;383:1207\u201317.","journal-title":"N Engl J Med"},{"key":"2982_CR38","doi-asserted-by":"publisher","first-page":"2530","DOI":"10.1200\/JCO.21.02752","volume":"40","author":"SI Ou","year":"2022","unstructured":"Ou SI, J\u00e4nne PA, Leal TA, Rybkin II, Sabari JK, Barve MA, et al. First-in-human phase I\/IB dose-finding study of adagrasib (MRTX849) in patients with advanced KRASG12C solid tumors (KRYSTAL-1). J Clin Oncol. 2022;40:2530\u20138.","journal-title":"J Clin Oncol"},{"key":"2982_CR39","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1038\/nature12796","volume":"503","author":"JM Ostrem","year":"2013","unstructured":"Ostrem JM, Peters U, Sos ML, Wells JA, Shokat KM. K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions. Nature. 2013;503:548\u201351.","journal-title":"Nature"},{"key":"2982_CR40","doi-asserted-by":"publisher","first-page":"604","DOI":"10.1126\/science.aad6204","volume":"351","author":"P Lito","year":"2016","unstructured":"Lito P, Solomon M, Li LS, Hansen R, Rosen N. Allele-specific inhibitors inactivate mutant KRAS G12C by a trapping mechanism. Science. 2016;351:604\u20138.","journal-title":"Science"},{"key":"2982_CR41","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1158\/2159-8290.CD-23-1138","volume":"14","author":"DA Rubinson","year":"2024","unstructured":"Rubinson DA, Tanaka N, Fece de la Cruz F, Kapner KS, Rosenthal MH, Norden BL, et al. Sotorasib is a pan-RASG12C inhibitor capable of driving clinical response in NRASG12C cancers. Cancer Discov. 2024;14:727\u201336.","journal-title":"Cancer Discov"},{"key":"2982_CR42","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1158\/1535-7163.MCT-24-0386","volume":"24","author":"A Tedeschi","year":"2025","unstructured":"Tedeschi A, Schischlik F, Rocchetti F, Popow J, Ebner F, Gerlach D, et al. Pan-KRAS inhibitors BI-2493 and BI-2865 display potent antitumor activity in tumors with KRAS wild-type allele amplification. Mol Cancer Ther. 2025;24:550\u201362.","journal-title":"Mol Cancer Ther"},{"key":"2982_CR43","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1038\/s41586-024-07205-6","volume":"629","author":"M Holderfield","year":"2024","unstructured":"Holderfield M, Lee BJ, Jiang J, Tomlinson A, Seamon KJ, Mira A, et al. Concurrent inhibition of oncogenic and wild-type RAS-GTP for cancer therapy. Nature. 2024;629:919\u201326.","journal-title":"Nature"},{"key":"2982_CR44","doi-asserted-by":"publisher","first-page":"994","DOI":"10.1158\/2159-8290.CD-24-0027","volume":"14","author":"J Jiang","year":"2024","unstructured":"Jiang J, Jiang L, Maldonato BJ, Wang Y, Holderfield M, Aronchik I, et al. Translational and therapeutic evaluation of RAS-GTP inhibition by RMC-6236 in RAS-driven cancers. Cancer Discov. 2024;14:994\u20131017.","journal-title":"Cancer Discov"},{"key":"2982_CR45","doi-asserted-by":"publisher","first-page":"956","DOI":"10.1158\/0008-5472.CAN-24-0323","volume":"85","author":"JB Foote","year":"2025","unstructured":"Foote JB, Mattox TE, Keeton AB, Chen X, Smith FT, Berry K, et al. A pan-RAS inhibitor with a unique mechanism of action blocks tumor growth and induces antitumor immunity in gastrointestinal cancer. Cancer Res. 2025;85:956\u201372.","journal-title":"Cancer Res"},{"key":"2982_CR46","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1182\/blood.2025030558","volume":"147","author":"B Popescu","year":"2026","unstructured":"Popescu B, Jones MF, Piao M, Tran E, Koh A, Lomeli I, et al. Multiselective RAS(ON) inhibition targets oncogenic RAS and overcomes RAS-mediated resistance to FLT3i and BCL2i in AML. Blood. 2026;147:276\u201389.","journal-title":"Blood"}],"container-title":["Leukemia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41375-026-02982-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41375-026-02982-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41375-026-02982-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T18:17:19Z","timestamp":1785521839000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41375-026-02982-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,2]]},"references-count":46,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["2982"],"URL":"https:\/\/doi.org\/10.1038\/s41375-026-02982-7","relation":{"is-basis-for":[{"id-type":"doi","id":"10.52843\/cassyni.0h9b0r","asserted-by":"object"}]},"ISSN":["0887-6924","1476-5551"],"issn-type":[{"value":"0887-6924","type":"print"},{"value":"1476-5551","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,2]]},"assertion":[{"value":"20 November 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 April 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 May 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 June 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"CCS reports research funding from Revolution Medicines, ERASCA, Abbvie; honoraria from Daiichi Sankyo; funding for clinical trials from Zentalis and Biomea; has served on advisory boards for Abbvie, Genentech, Servier and Biomea; and has served as a consultant for Astellas. ET reports research funding from AstraZeneca, Genentech, Prelude, Rigel, Schrodinger; funding for clinical trials from Incyte; and has served as a consultant for Abbvie, Astellas, Daiichi-Sankyo, Incyte, Rigel, Servier and Syndax.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}]}}